Cancer Drug Decreases Recurrence of Gastrointestinal Stromal Tumors
The Bottom Line
Results of a randomized phase III clinical trial show that targeted therapy with the drug imatinib mesylate(Gleevec) reduces disease recurrence following surgery to remove a localized gastrointestinal stromal tumor.
The Whole Story
Each year in the United States, approximately 3,000 to 4,000 people are diagnosed with gastrointestinal stromal tumor (GIST), a type of cancer that is usually found in the stomach or the small intestine. Surgery is the main form of treatment for localized, primary GIST, but the tumor often recurs, or comes back, following surgery. Post-surgical, or adjuvant, treatment with standard chemotherapy drugs is not effective in reducing the recurrence of GIST. Because previous studies had shown that targeted therapy with the drug imatinib mesylate (Gleevec) was effective in treating metastatic GIST, researchers wanted to know whether adjuvant therapy with imatinib would reduce localized GIST recurrence.
Therefore, a team of researchers, led by the American College of Surgeons Oncology Group (ACOSOG), which is an NCI Clinical Trials Cooperative Group, conducted a randomized clinical trial in which 713 patients were randomly assigned to receive either imatinib or a placebo after surgery to remove localized GIST. The patients took imatinib or the placebo orally once a day for a year. A data monitoring committee conducted interim analyses at 6-month intervals to see if signs of imatinib's effectiveness or ineffectiveness were beginning to emerge. The trial began enrolling patients in 2002.
In April 2007, the trial was stopped early on the recommendation of the data monitoring committee because an interim analysis had shown that imatinib was effective in reducing the rate of GIST recurrence. In March 2009, initial results of the trial were published.
The results showed that, at a median follow-up of about 20 months, 8 percent of the patients in the imatinib group had had a recurrence or died, compared with 20 percent of the patients in the placebo group. The occurrence of harmful side effects from imatinib was low, and the types of side effects noted were similar to those observed in patients treated with imatinib for chronic myelogenous leukemia and metastatic GIST. The death rates in the imatinib group and the placebo group were very low and similar, although the follow-up time for assessing survival was very short and the study allowed patients whose cancer recurred while on study to cross-over to receive imatinib if they had been initially randomly assigned to receive placebo.
"The results," noted principal investigator Dr. Ronald DeMatteo, of Memorial Sloan-Kettering Cancer Center in New York, "have major implications for patients with primary GIST." In December 2008, the Food and Drug Administration approved the use of imatinib as adjuvant therapy for adult patients after complete resection of localized, primary GIST.
NCI Press Release: http://www.cancer.gov/newscenter/pressreleases/GISTtrial
Publication: DeMatteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373(9669): 1097-1104.
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